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Tracking post-infectious fatigue in clinic using routine Lab tests.
Harvey, JM, Broderick, G, Bowie, A, Barnes, ZM, Katz, BZ, O'Gorman, MRG, Vernon, SD, Fletcher, MA, Klimas, NG, Taylor, R
BMC pediatrics. 2016;16:54
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Chronic fatigue syndrome (CFS) is a complex disease with many different symptoms and there are no definitive tests for diagnosis. This cohort study of 301 adolescents, who had suffered a viral infection, aimed to analyse several commonly used biological markers to determine who may experience CFS symptoms. The results showed variations in several biomarkers, however, decreases in hormones related to the stress response were highly predictive of CFS. Sex hormones and the proportion of immune cells were also markedly disrupted. It was concluded that assessing stress hormones, sex hormones and the proportion of immune cells could be used to diagnose CFS following a viral infection. This study could be used by healthcare professionals to understand that several commonly tested biomarkers could be potentially used to diagnose post-viral CFS.
Abstract
BACKGROUND While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. METHODS Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis. Classification models separating PI-CFS from controls were constructed at each time point using stepwise subset selection. RESULTS Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups. CONCLUSIONS Preliminary results suggest that serial assessment of stress and sex hormones as well as the relative proportion of innate immune cells measured using standard clinical laboratory tests may support the diagnosis of PI-CFS in adolescents with IM.
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Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study.
Wesa, KM, Cunningham-Rundles, S, Klimek, VM, Vertosick, E, Coleton, MI, Yeung, KS, Lin, H, Nimer, S, Cassileth, BR
Cancer immunology, immunotherapy : CII. 2015;64(2):237-47
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Myelodysplastic syndromes (MDS) are a group of bone marrow stem cell disorders characterized by ineffective red blood cell production, a reduction in mature blood cells and may progress to acute myelogenous leukaemia (AML). Low levels and poor function of white blood cells, a key part of the immune system, are a common feature of MDS and this increases the risk of serious infection, the most common cause of death in lower-risk MDS patients. Maitake had previously been shown to enhance blood forming cells and was therefore thought to be of potential benefit for MDS patients. The aim of this phase II, open-label, non-randomized, safety and efficacy trial was to assess white blood cells function in lower-risk MDS patients. 18 untreated patients received Maitake extract at 6 mg/kg daily for 12 weeks. The function of two types of white blood cells, neutrophils and monocytes,increased after 12 weeks of maitake administration. Maitake was generally well tolerated although a mild increase in eosinophils, a type of white blood cells associated with allergies, was noted in four patients, and two of these patients also experienced mild diarrhoea. The authors concluded that maitake beta-glucan consumption improves white blood cell (neutrophil and monocyte) function in lower-risk MDS patients and may enhance immune responses against bacterial infection. They point out that one limitation of their trial was a lack of control group and that larger studies are needed to confirm the potential benefits of maitake.
Abstract
BACKGROUND Myelodysplastic syndromes (MDS) are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia. Maitake mushroom beta-glucan, a dietary supplement, stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury. This phase II trial examined the effects of Maitake on innate immune function in MDS. METHODS Myelodysplastic syndromes patients with International Prognostic Scoring System Low- and Intermediate-1-risk disease received oral Maitake extract at 3 mg/kg twice daily for 12 weeks. Primary endpoints included neutrophil count and function tested as endogenous or stimulated neutrophil production of reactive oxygen species (ROS) by flow cytometry compared with age-matched healthy controls (HC). ROS activators were Escherichia coli, phorbol ester, and the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Complete blood counts, chemistry panels, iron studies, and monocyte function were evaluated. RESULTS Of 21 patients enrolled, 18 completed the study and were evaluable. Maitake increased endogenous (basal) neutrophil (p = 0.005) and monocyte function (p = 0.021). Pre-treatment monocyte response to E. coli was reduced in MDS patients compared with HC (p = 0.002) and increased (p = 0.0004) after treatment. fMLP-stimulated ROS production response also increased (p = 0.03). Asymptomatic eosinophilia occurred in 4 patients (p = 0.014). Other changes in albumin, hemoglobin, and total protein were not clinically relevant. CONCLUSIONS Maitake was well tolerated. Enhanced in vitro neutrophil and monocyte function following treatment demonstrate that Maitake has beneficial immunomodulatory potential in MDS. Further study is warranted.
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A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects.
Deng, G, Lin, H, Seidman, A, Fornier, M, D'Andrea, G, Wesa, K, Yeung, S, Cunningham-Rundles, S, Vickers, AJ, Cassileth, B
Journal of cancer research and clinical oncology. 2009;135(9):1215-21
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Grifola frondosa (maitake) is a medicinal mushroom which has been shown to be able to modulate the immune system. Many cancer patients use maitake extracts, however, evidence from clinical trials is lacking. This open label trial set out to determine the optimal dose of maitake extract based on possible toxic effects and blood parameters reflecting the state of the immune system. Eligible patients (post-menopausal women with previously treated breast cancer who were free of disease) were sequentially allocated to one of five groups (six subjects in each group) who received 0.2, 1, 3, 6 and 10 mg/kg of liquid maitake extract, respectively, daily for three weeks. Bloods were taken prior to the study beginning and on days 7, 14 and 21. No adverse effects or toxicities were observed. There were statistically significant dose response relationships for 25 out of the 146 parameters measured, with a stimulatory effect on some parameters, and a suppressing on others. The authors concluded that maitake was well tolerated and was associated with significant effects on immune balance, however, the effects were complex and depended on the different cell types and cytokines (specific signalling molecules of the immune system) evaluated, suggesting that maitake should be seen as an immune “modulator” rather than “enhancer”. The study was not designed to evaluate clinical efficacy of maitake.
Abstract
BACKGROUND Cancer patients commonly use dietary supplements to "boost immune function". A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown. METHODS In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days -7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability. RESULTS No dose-limiting toxicity was encountered. Two patients withdrew prior to completion of the study due to grade I possibly related side effects: nausea and joint swelling in one patient; rash and pruritus in the second. There was a statistically significant association between Maitake and immunologic function (p < 0.0005). Increasing doses of Maitake increased some immunologic parameters and depressed others; the dose-response curves for many endpoints were non-monotonic with intermediate doses having either immune enhancing or immune suppressant effects compared with both high and low doses. CONCLUSIONS Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. Cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function.